Impact of dolutegravir and efavirenz on immune recovery markers: results from a randomized clinical trial

Objectives: CD4/CD8 ratio and CD4(+) T-cell percentage (CD4%) predicts the risk of AIDS and non-AIDS events. Multiple T-cell marker recovery (MTMR) has been proposed as the most complete level of immune reconstitution. We quantified differences in the CD4/CD8 ratio, CD4% recovery and MTMR after starting HIV-1 treatment with dolutegravir/abacavir/lamivudine vs. efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC). Methods: Exploratory post hoc analysis of the SINGLE study, a randomized double-blind, clinical trial. Percentage differences and corresponding precision based on 95% confidence intervals, and p values were calculated for CD4/CD8 ratio normalization, CD4% normalization and the achievement of MTMR. Cox models taking into account competing risks were used to estimate sub-hazard ratios when comparing the times to normalization of the CD4/CD8 ratio and the CD4% by treatment arm. Results: Data from 833 participants were analysed (414 in the dolutegravir/abacavir/lamivudine arm). There were no statistically significant differences in the proportion of patients who reached a CD4/CD8 ratio >= 0.5 at weeks 48 and 96. However, at week 96, the proportion of patients with a CD4/CD8 ratio >= 1 was higher in the EFV-TDF-FTC group (difference, 11.70; 95% confidence interval, 4.49-18.91; p 0.002). The decrease from baseline in CD8(+) cell count was consistently greater in the EFV-TDF-FTC arm. Analysis of CD4(+) percentages showed no significant differences during the study. The proportion of patients attaining a MTMR was higher in the EFV-TDF-FTC group, although the difference was only statistically significant at week 96 (p 0.001). Conclusions: EFV-TDF-FTC showed significantly greater increases in CD4/CD8 ratio >= 1.0 or MTMR beyond treatment week 96. Additional studies are necessary to better understand the impact of these findings. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.